Flower lose, a cell fitness marker, predicts COVID-19 prognosis.


Journal

EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380

Informations de publication

Date de publication:
08 11 2021
Historique:
revised: 14 09 2021
received: 10 11 2020
accepted: 16 09 2021
pubmed: 19 10 2021
medline: 11 11 2021
entrez: 18 10 2021
Statut: ppublish

Résumé

Risk stratification of COVID-19 patients is essential for pandemic management. Changes in the cell fitness marker, hFwe-Lose, can precede the host immune response to infection, potentially making such a biomarker an earlier triage tool. Here, we evaluate whether hFwe-Lose gene expression can outperform conventional methods in predicting outcomes (e.g., death and hospitalization) in COVID-19 patients. We performed a post-mortem examination of infected lung tissue in deceased COVID-19 patients to determine hFwe-Lose's biological role in acute lung injury. We then performed an observational study (n = 283) to evaluate whether hFwe-Lose expression (in nasopharyngeal samples) could accurately predict hospitalization or death in COVID-19 patients. In COVID-19 patients with acute lung injury, hFwe-Lose is highly expressed in the lower respiratory tract and is co-localized to areas of cell death. In patients presenting in the early phase of COVID-19 illness, hFwe-Lose expression accurately predicts subsequent hospitalization or death with positive predictive values of 87.8-100% and a negative predictive value of 64.1-93.2%. hFwe-Lose outperforms conventional inflammatory biomarkers and patient age and comorbidities, with an area under the receiver operating characteristic curve (AUROC) 0.93-0.97 in predicting hospitalization/death. Specifically, this is significantly higher than the prognostic value of combining biomarkers (serum ferritin, D-dimer, C-reactive protein, and neutrophil-lymphocyte ratio), patient age and comorbidities (AUROC of 0.67-0.92). The cell fitness marker, hFwe-Lose, accurately predicts outcomes in COVID-19 patients. This finding demonstrates how tissue fitness pathways dictate the response to infection and disease and their utility in managing the current COVID-19 pandemic.

Identifiants

pubmed: 34661368
doi: 10.15252/emmm.202013714
pmc: PMC8573598
doi:

Substances chimiques

Biomarkers 0

Types de publication

Journal Article Observational Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e13714

Subventions

Organisme : NCI NIH HHS
ID : P30 CA014520
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA228991
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM104942
Pays : United States
Organisme : Fundação para a Ciência e a Tecnologia
ID : BD/135367/2017
Organisme : NIGMS NIH HHS
ID : P20 GM103434
Pays : United States
Organisme : Thelma Newmeyer Corman Chair in Cancer Research
Organisme : Champalimaud Foundation
Organisme : NCI NIH HHS
ID : R01 CA259599
Pays : United States
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : KFO309 TP08
Organisme : Botnar Research Centre for Child Health (BRCCH)
ID : FTC-2020-10
Organisme : NIH/NIGMS
ID : P20GM103434
Organisme : La Caixa
ID : LCF/BQ/PR20/11770006
Organisme : Fundação para a Ciência e a Tecnologia
Organisme : NIH/NIGMS
ID : P20GM121322
Organisme : Novo Nordisk Foundation
ID : NNF17CC0027852
Organisme : ERC
Organisme : Seeds of Science, UAMS
Organisme : German Center for Lung Research (DZL)
Organisme : DFG Collaborative Research Center
ID : SFB1021
Organisme : Honorable Tina Brozman Foundation for Ovarian Cancer Research
Organisme : NIH HHS
ID : P50 SPORE CA228991
Pays : United States
Organisme : SNSF
Organisme : Swiss Cancer League
Organisme : Fundação para a Ciência e a Tecnologia
ID : SFRH/BD/139138/2018
Organisme : Fundamental Mandates (Stichting tegen Kanker-Fondation contre le Cancer)
Organisme : Adelson Medical Research Foundation
Organisme : NIH/NIGMS
ID : 2U54 GM104942-03
Organisme : Lundbeck Foundation
ID : R313-2019-421
Organisme : VCU Commercialization Fund
Organisme : National Science Foundation
ID : NSF/1920920
Organisme : NIGMS NIH HHS
ID : P20 GM130423
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM121322
Pays : United States
Organisme : Josef Steiner Cancer Research Foundation
Organisme : DFG Clinical Research Unit
ID : KFO 309
Organisme : Fundação para a Ciência e a Tecnologia
ID : 2020.05319.BD
Organisme : FIS (Ministry of Health), Madrid, Spain
ID : PI17/01981
Organisme : National Science Foundation
ID : NSF/1761792

Informations de copyright

© 2021 The Authors. Published under the terms of the CC BY 4.0 license.

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Auteurs

Michail Yekelchyk (M)

Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.

Esha Madan (E)

Champalimaud Centre for the Unknown, Lisbon, Portugal.

Jochen Wilhelm (J)

Universities Giessen & Marburg Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.
Institute for Lung Health (ILH), Universities Giessen & Marburg Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University Giessen, Giessen, Germany.

Kirsty R Short (KR)

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld, Australia.

António M Palma (AM)

Champalimaud Centre for the Unknown, Lisbon, Portugal.

Linbu Liao (L)

Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen N, Denmark.

Denise Camacho (D)

Champalimaud Centre for the Unknown, Lisbon, Portugal.

Everlyne Nkadori (E)

Department of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.

Michael T Winters (MT)

Department of Microbiology, Immunology & Cell Biology and WVU Cancer Institute, West Virginia University, Morgantown, WV, USA.

Emily S Rice (ES)

Department of Microbiology, Immunology & Cell Biology and WVU Cancer Institute, West Virginia University, Morgantown, WV, USA.

Inês Rolim (I)

Champalimaud Centre for the Unknown, Lisbon, Portugal.

Raquel Cruz-Duarte (R)

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.

Christopher J Pelham (CJ)

Eurofins Panlabs Inc., St. Charles, MO, USA.

Masaki Nagane (M)

Department of Biochemistry, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.

Kartik Gupta (K)

Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.

Sahil Chaudhary (S)

Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.

Thomas Braun (T)

Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Member of the German Center for Cardiovascular Research (DZHK), Greifswald, Germany.

Raghavendra Pillappa (R)

Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.

Mark S Parker (MS)

Department of Diagnostic Radiology and Internal Medicine, Early Detection Lung Cancer Screening Program, Thoracic Imaging Division, Thoracic Imaging Fellowship Program, VCU Health Systems, Richmond, VA, USA.

Thomas Menter (T)

Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.

Matthias Matter (M)

Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.

Jasmin Dionne Haslbauer (JD)

Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.

Markus Tolnay (M)

Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.

Kornelia D Galior (KD)

Department of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.

Kristina A Matkwoskyj (KA)

Department of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.

Stephanie M McGregor (SM)

Department of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.

Laura K Muller (LK)

Department of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.

Emad A Rakha (EA)

Division of Cancer and Stem Cells, Department of Pathology, School of Medicine, Nottingham University Hospitals, University of Nottingham, Nottingham, UK.

Antonio Lopez-Beltran (A)

Champalimaud Centre for the Unknown, Lisbon, Portugal.
Department of Morphological Sciences, Cordoba University, Cordoba, Spain.

Ronny Drapkin (R)

Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Graduate Program in Cell and Molecular Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Maximilian Ackermann (M)

Institute of Pathology and Molecular Pathology, Helios University Clinic Wuppertal, University of Witten/Herdecke, Wuppertal, Germany.
Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Paul B Fisher (PB)

Department of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Department of Human and Molecular Genetics, Institute of Molecular Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.

Steven R Grossman (SR)

Department of Internal Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
University of Southern California, Los Angeles, CA, USA.

Andrew K Godwin (AK)

Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
University of Kansas Cancer Center, Kansas City, KS, USA.

Arutha Kulasinghe (A)

The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Qld, Australia.

Ivan Martinez (I)

Department of Microbiology, Immunology & Cell Biology and WVU Cancer Institute, West Virginia University, Morgantown, WV, USA.

Clay B Marsh (CB)

Department of Microbiology, Immunology & Cell Biology and WVU Cancer Institute, West Virginia University, Morgantown, WV, USA.

Benjamin Tang (B)

Department of Intensive Care Medicine, Nepean Hospital, Penrith, NSW, Australia.

Max S Wicha (MS)

Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.

Kyoung Jae Won (KJ)

Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen N, Denmark.
Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, University of Copenhagen, Copenhagen N, Denmark.

Alexandar Tzankov (A)

Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.

Eduardo Moreno (E)

Champalimaud Centre for the Unknown, Lisbon, Portugal.

Rajan Gogna (R)

Champalimaud Centre for the Unknown, Lisbon, Portugal.
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen N, Denmark.
Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, University of Copenhagen, Copenhagen N, Denmark.

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